St George’s, University of London has signed an exclusive worldwide licensing agreement with rare-disease research-and-development firm Orphan Technologies Ltd to develop new therapies for deadly metabolic disorders.

St George’s and Orphan aim to develop therapies based on an innovative and highly specialised cell-based enzyme-replacement technology, called Erythrocyte Encapsulated (EE) technology.

Their primary goal is to accelerate the development of an investigational therapy for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a progressive disease that kills patients at an average age of 38. Upon approval, the new enzyme-replacement therapy would be the first approved drug treatment for a mitochondrial disease.

MNGIE is caused by a defect in the gene responsible for production of the enzyme thymidine phosphorylase (TP). Without this enzyme, mitochondria – the parts of the body’s cells that create energy for the cells – cannot function properly, leading to problems with the nervous system and skeletal muscle. Symptoms of MNGIE include diarrhoea, constipation, gastroparesis, nausea, vomiting, weight loss, muscle weakness and nerve damage leading to loss of sensation and abnormal eye movements.

Globally, only 200 cases of MNGIE have been identified, but these are increasing and experts believe it has been underdiagnosed. The only current potential cure is a stem cell transplant technique, but this carries a high risk of death and most patients are ineligible as recruitment is restricted only to those with an optimal matched donor and without irreversible end-stage disease.

The investigational therapy for MNGIE is called Erythrocyte Encapsulated Thymidine Phosphorylase (EE-TP), which is based on introducing TP directly into patients' red blood cells (erythrocytes). This encapsulation technology has the advantages of increasing the period the enzyme is most effective for and minimising immunogenic reactions.

Several patients with urgent medical needs have already been effectively treated with EE-TP through compassionate use treatment. Administration of EE-TP was reported to be effective in reducing or eliminating the elevated plasma and urine concentrations of thymidine and deoxyuridine, toxic substances that accumulate in tissues of MNGIE patients. Clinical improvements have also been reported, with a reduction in the number of nausea and vomiting attacks, a reduction in weight loss, and an improvement in distal sensation in hands and fingers.

Dr Bridget Bax, head of the St George’s team and one of the world’s leading authorities on MNGIE, said: “MNGIE is a relentlessly progressive degenerative disease and for a majority of patients there are no treatment options other than supportive care. Our team is committed to addressing the unmet needs of these patients.

“Under the licensing agreement with Orphan, we intend to combine our strengths to accelerate the regulatory development of EE-TP. Our ultimate hope is that EE-TP will benefit patients with MNGIE and that patients globally have equitable access.”

Josef Rosenberg, director of Orphan Technologies, said: "We are excited to enter into this licensing agreement and expand our pipeline with this pioneering technology from St George's, University of London. Orphan Technologies is committed to the development of innovative therapies for patients suffering from devastating ultra-rare disorders with unmet medical needs, and this agreement is well aligned with this objective. EE-TP has shown very promising clinical data results in compassionate use treatment for MNGIE patients. The St George's team, led by Dr Bridget Bax, brings unique experience with the EE-TP technology; we are proud to be working with them and together aim to bring hope to the MNGIE population.”

EE-TP has been granted orphan drug status in Europe and the United States. This is given to drugs being developed to treat rare conditions, and makes the regulatory process simpler than for common diseases.

Under the agreement with St George’s, Orphan Technologies has also licensed rights for the development of a new enzyme-replacement therapy for severe combined immunodeficiency (SCID) due to adenosine deaminase deficiency (ADA-SCID), another rare, fatal metabolic disease. SCID is a severe form of hereditary immunodeficiency, which makes patients extremely vulnerable to repeated and persistent infections that can be very serious and life threatening. If not treated in a way that restores immune function, children with SCID usually live only a year or two. The novel therapy, Erythrocyte Encapsulated Adenosine Deaminase (EE-ADA), has been proved efficient and safe, as reported in the treatment of an ADA-SCID patient for more than 15 years.